Crotonase catalysis enables flexible production of functionalized prolines and carbapenams.
The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malon...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797101236113113088 |
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| author | Hamed, R Henry, L Gomez-Castellanos, JR Mecinović, J Ducho, C Sorensen, J Claridge, T Schofield, C |
| author_facet | Hamed, R Henry, L Gomez-Castellanos, JR Mecinović, J Ducho, C Sorensen, J Claridge, T Schofield, C |
| author_sort | Hamed, R |
| collection | OXFORD |
| description | The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers. |
| first_indexed | 2024-03-07T05:48:56Z |
| format | Journal article |
| id | oxford-uuid:e82c2e7c-28c1-4aca-96b8-5f88ae5dd3f1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:48:56Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:e82c2e7c-28c1-4aca-96b8-5f88ae5dd3f12022-03-27T10:44:42ZCrotonase catalysis enables flexible production of functionalized prolines and carbapenams.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e82c2e7c-28c1-4aca-96b8-5f88ae5dd3f1EnglishSymplectic Elements at Oxford2012Hamed, RHenry, LGomez-Castellanos, JRMecinović, JDucho, CSorensen, JClaridge, TSchofield, CThe biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers. |
| spellingShingle | Hamed, R Henry, L Gomez-Castellanos, JR Mecinović, J Ducho, C Sorensen, J Claridge, T Schofield, C Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title | Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title_full | Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title_fullStr | Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title_full_unstemmed | Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title_short | Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. |
| title_sort | crotonase catalysis enables flexible production of functionalized prolines and carbapenams |
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